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NCI Launches First-Ever Study to Determine if Biomarkers Can Help Guide Treatment for Lung Cancer

Today a large, national clinical trial for non-small cell lung cancer was launched to validate whether a biomarker can predict clinical benefit in the treatment of this disease. Biomarkers, which are molecules found in the body that can signal an abnormal process or disease, would identify a target, known as epidermal growth factor receptor (EGFR). This receptor can be increased in some lung cancers due to the presence of extra copies of its coding gene. These extra copies can result in activation of tumor growth, so drugs that block this activation could have a significant impact on lung cancer treatment. This study, sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, is called MARVEL (Marker Validation for Erlotinib in Lung Cancer) and will attempt to definitively establish the future value of selecting patients for treatment based on the presence or absence of EGFR activation.

Approximately 1,200 lung cancer patients will be tested for the status of this biomarker, and then will be randomly assigned to treatment based on the test results. Both EGFR-positive and EGFR-negative patients will receive either the chemotherapy drugs erlotinib (Tarceva, Genentech) or pemetrexed (Alimta, Eli Lilly) after they have received their initial, standard chemotherapy. Erlotinib specifically targets EGFR, whereas pemetrexed blocks tumor cell growth by another mechanism.

It is hypothesized that erlotinib will be superior in the patients with EGFR-positive lung cancer, whereas pemetrexed would be favored in patients with EGFR-negative lung cancer, based on knowledge from earlier, smaller studies. MARVEL will incorporate genetic studies for erlotinib and pemetrexed that will be important to further identify patients with different sensitivity and toxicity profiles to these therapies.

Lung cancer is expected to claim 161,840 lives in 2008, and 215,020 people are expected to be diagnosed with the disease this year, making it the number one cancer killer. Non-small cell lung cancer represents about 85 to 90 percent of all lung cancers.

"Because lung cancer is such a lethal disease and because it is particularly difficult to treat, especially if diagnosed in its later stages, the MARVEL trial is of major importance because it could define, based on a single test, the best therapy for this disease. The future of moving highly targeted agents from the lab to the clinic will be heavily dependent on biomarkers for patient selection," said NCI director John E. Niederhuber, M.D.

Both erlotinib and pemetrexed are approved treatments for advanced NSCLC. Among the factors that appear to influence responsiveness to erlotinib, in addition to the level of EGFR activation, are whether the resulting cancer cells are classified as adenocarcinomas (as opposed to squamous or other types of cell), female gender, Asian ethnicity, and whether the patient was ever a smoker. However, no forward-looking study has been performed to definitively address which factors are most important.

MARVEL, also known as N0723, is a phase III study that will be led by the North Central Cancer Treatment Group (NCCTG) and include many other NCI-sponsored clinical trial groups. The trial will enroll patients over a four year period and test them for EGFR status. It will randomly assign about 950 of the 1,200 tested patients to the treatment protocol (assuming that 80 percent of the tests will successfully allow classification of patients as either EGFR-positive or EGFR-negative), and, after a minimum of one to two years of follow-up, accrue data on disease-free and overall patient survival rates as well as determine if markers are good predictive and prognostic tools. It will also establish whether erlotinib provides a meaningful benefit over the patients’ initial, standard chemotherapy.

This trial is the outcome of a unique and innovative collaboration, formed in 2006, called the Oncology Biomarkers Qualification Initiative (OBQI) between NCI, the U.S. Food and Drug Administration (FDA), and the Centers for Medicare and Medicaid Services. OBQI was designed to qualify biomarkers for use in clinical trials and, ultimately, to speed better agents to cancer patients.

"The MARVEL trial is unique and an important first because it is an outgrowth of specific NCI initiatives designed to advance lung cancer therapies and received broad input from the FDA, NCI cooperative groups, the biomarker industry, and the pharmaceutical industry," said Alex A. Adjei, M.D., Ph.D., senior vice president of Clinical Research at Roswell Park Cancer Institute, Buffalo, N.Y., and chair of the study.

In addition to being chaired by the NCCTG, the trial represents a collaborative effort of many of NCI’s cooperative groups who perform lung cancer research including the Cancer and Leukemia Group B (CALGB), the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG) and the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), as well as industry partners. For more information on MARVEL, please go tohttp://www.clinicaltrials.gov/ct2/show/NCT00738881?id=N0723&rank=1#desc.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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